Cargando…
Recombinant Adeno-Associated Virus-mediated rescue of function in a mouse model of Dopamine Transporter Deficiency Syndrome
Dopamine Transporter Deficiency Syndrome (DTDS) is a rare autosomal recessive disorder caused by loss-of-function mutations in dopamine transporter (DAT) gene, leading to severe neurological disabilities in children and adults. DAT-Knockout (DAT-KO) mouse is currently the best animal model for this...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5394687/ https://www.ncbi.nlm.nih.gov/pubmed/28417953 http://dx.doi.org/10.1038/srep46280 |
_version_ | 1783229763423305728 |
---|---|
author | Illiano, P. Bass, C.E. Fichera, L. Mus, L. Budygin, E.A. Sotnikova, T.D. Leo, D. Espinoza, S. Gainetdinov, R.R. |
author_facet | Illiano, P. Bass, C.E. Fichera, L. Mus, L. Budygin, E.A. Sotnikova, T.D. Leo, D. Espinoza, S. Gainetdinov, R.R. |
author_sort | Illiano, P. |
collection | PubMed |
description | Dopamine Transporter Deficiency Syndrome (DTDS) is a rare autosomal recessive disorder caused by loss-of-function mutations in dopamine transporter (DAT) gene, leading to severe neurological disabilities in children and adults. DAT-Knockout (DAT-KO) mouse is currently the best animal model for this syndrome, displaying functional hyperdopaminergia and neurodegenerative phenotype leading to premature death in ~36% of the population. We used DAT-KO mouse as model for DTDS to explore the potential utility of a novel combinatorial adeno-associated viral (AAV) gene therapy by expressing DAT selectively in DA neurons and terminals, resulting in the rescue of aberrant striatal DA dynamics, reversal of characteristic phenotypic and behavioral abnormalities, and prevention of premature death. These data indicate the efficacy of a new combinatorial gene therapy aimed at rescuing DA function and related phenotype in a mouse model that best approximates DAT deficiency found in DTDS. |
format | Online Article Text |
id | pubmed-5394687 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-53946872017-04-20 Recombinant Adeno-Associated Virus-mediated rescue of function in a mouse model of Dopamine Transporter Deficiency Syndrome Illiano, P. Bass, C.E. Fichera, L. Mus, L. Budygin, E.A. Sotnikova, T.D. Leo, D. Espinoza, S. Gainetdinov, R.R. Sci Rep Article Dopamine Transporter Deficiency Syndrome (DTDS) is a rare autosomal recessive disorder caused by loss-of-function mutations in dopamine transporter (DAT) gene, leading to severe neurological disabilities in children and adults. DAT-Knockout (DAT-KO) mouse is currently the best animal model for this syndrome, displaying functional hyperdopaminergia and neurodegenerative phenotype leading to premature death in ~36% of the population. We used DAT-KO mouse as model for DTDS to explore the potential utility of a novel combinatorial adeno-associated viral (AAV) gene therapy by expressing DAT selectively in DA neurons and terminals, resulting in the rescue of aberrant striatal DA dynamics, reversal of characteristic phenotypic and behavioral abnormalities, and prevention of premature death. These data indicate the efficacy of a new combinatorial gene therapy aimed at rescuing DA function and related phenotype in a mouse model that best approximates DAT deficiency found in DTDS. Nature Publishing Group 2017-04-18 /pmc/articles/PMC5394687/ /pubmed/28417953 http://dx.doi.org/10.1038/srep46280 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Illiano, P. Bass, C.E. Fichera, L. Mus, L. Budygin, E.A. Sotnikova, T.D. Leo, D. Espinoza, S. Gainetdinov, R.R. Recombinant Adeno-Associated Virus-mediated rescue of function in a mouse model of Dopamine Transporter Deficiency Syndrome |
title | Recombinant Adeno-Associated Virus-mediated rescue of function in a mouse model of Dopamine Transporter Deficiency Syndrome |
title_full | Recombinant Adeno-Associated Virus-mediated rescue of function in a mouse model of Dopamine Transporter Deficiency Syndrome |
title_fullStr | Recombinant Adeno-Associated Virus-mediated rescue of function in a mouse model of Dopamine Transporter Deficiency Syndrome |
title_full_unstemmed | Recombinant Adeno-Associated Virus-mediated rescue of function in a mouse model of Dopamine Transporter Deficiency Syndrome |
title_short | Recombinant Adeno-Associated Virus-mediated rescue of function in a mouse model of Dopamine Transporter Deficiency Syndrome |
title_sort | recombinant adeno-associated virus-mediated rescue of function in a mouse model of dopamine transporter deficiency syndrome |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5394687/ https://www.ncbi.nlm.nih.gov/pubmed/28417953 http://dx.doi.org/10.1038/srep46280 |
work_keys_str_mv | AT illianop recombinantadenoassociatedvirusmediatedrescueoffunctioninamousemodelofdopaminetransporterdeficiencysyndrome AT bassce recombinantadenoassociatedvirusmediatedrescueoffunctioninamousemodelofdopaminetransporterdeficiencysyndrome AT ficheral recombinantadenoassociatedvirusmediatedrescueoffunctioninamousemodelofdopaminetransporterdeficiencysyndrome AT musl recombinantadenoassociatedvirusmediatedrescueoffunctioninamousemodelofdopaminetransporterdeficiencysyndrome AT budyginea recombinantadenoassociatedvirusmediatedrescueoffunctioninamousemodelofdopaminetransporterdeficiencysyndrome AT sotnikovatd recombinantadenoassociatedvirusmediatedrescueoffunctioninamousemodelofdopaminetransporterdeficiencysyndrome AT leod recombinantadenoassociatedvirusmediatedrescueoffunctioninamousemodelofdopaminetransporterdeficiencysyndrome AT espinozas recombinantadenoassociatedvirusmediatedrescueoffunctioninamousemodelofdopaminetransporterdeficiencysyndrome AT gainetdinovrr recombinantadenoassociatedvirusmediatedrescueoffunctioninamousemodelofdopaminetransporterdeficiencysyndrome |